Sequence-Defined Polymers via Orthogonal Allyl Acrylamide Building Blocks

Biological systems have long recognized the importance of macromolecular diversity and have evolved efficient processes for the rapid synthesis of sequence-defined biopolymers. However, achieving sequence control via synthetic methods has proven to be a difficult challenge. Herein we describe efforts to circumvent this difficulty via the use of orthogonal allyl acrylamide building blocks and a liquid-phase fluorous support for the de novo design and synthesis of sequence-specific polymers. We demonstrate proof-of-concept via synthesis and characterization of two sequence-isomeric 10-mer polymers. ¹H NMR and LCMS were used to confirm their chemical structure while tandem MS was used to confirm sequence identity. Further validation of this methodology was provided via the successful synthesis of a sequence-specific 16-mer polymer incorporating nine different monomers. This strategy thus shows promise as an efficient approach for the assembly of sequence-specific functional polymers

Ultrafast Photoinduced Electron Transfer between an Incarcerated Donor and a Free Acceptor in Aqueous Solution

Supramolecular photoinduced electron transfer dynamics between coumarin 153 (C153) and 4,4′-dimethyl viologen dichloride (MV²⁺) across the molecular barrier of a host molecule, octa acid (OA), has been investigated with femtosecond time resolution. The ultrafast electron transfer from C153 to MV²⁺ followed excitation with 150 fs laser pulses at a wavelength of 390 nm despite the fact that C153 was incarcerated within an OA₂ capsule. As a result, the photoexcited coumarin did not show any of the typical relaxation dynamics that is usually observed in free solution. Instead, the excited electron was transferred across the molecular wall of the capsuleplex within 20 ps. Likewise, the lifetime of the charge transfer state was short (724 ps), and electron back-transfer reestablished the ground state of the system within 1 ns, showing strong electronic coupling among the excited electron donor, host, and acceptor. When the donor was encapsulated into the host molecule, the electron transfer process showed significantly accelerated dynamics and essentially no solvent relaxation compared with that in free solution. The study was also extended to <i>N</i>-methylpyridinium iodide as the acceptor with similar results

CIDEP from a Polarized Ketone Triplet State Incarcerated within a Nanocapsule to a Nitroxide in the Bulk Aqueous Solution

Thioxanthone and benzil derivatives were incarcerated into an octa acid nanocapsule. Photoexcitation of these ketones generated electronic triplet excited states, which become efficiently quenched by positively charged nitroxides adsorbed outside on the external surface of the negatively charged nanocapsule. Although the triplet excited ketone and quencher are separated by a molecular wall (nanocapsule), quenching occurs on the nanosecond time scale and generates spin-polarized nitroxides, which were observed by time-resolved EPR spectroscopy. Because opposite signs of spin polarization of nitroxides were observed for thioxanthone and benzil derivatives, it is proposed that the electron spin polarization transfer mechanism of spin-polarized triplet states to nitroxides is the major mechanism of generating nitroxide polarization

Sequence-Defined Backbone Modifications Regulate Antibacterial Activity of OligoTEAs

In response to the urgent need for new antibiotic development strategies, antimicrobial peptides (AMPs) and other synthetic polymers are being actively investigated as promising alternatives to traditional antibiotics. Although most AMPs display lytic activity against several types of bacteria, they have poor toxicology profiles and are susceptible to proteolysis <i>in vivo</i>. While many synthetic variants have been created to mimic AMPs by tuning the hydrophobic to cationic ratio of the side-chain groups, few have decoupled the effects of charge from hydrophobicity in discrete systems, and none have investigated the effect of backbone hydrophobicity. We recently developed a rapid and efficient approach for the assembly of synthetic sequence-defined oligothioetheramides (oligoTEAs) that are resistant to protease activity. Our oligoTEA assembly scheme allows direct access to the oligomer backbone, which enables precise tuning of oligoTEA hydrophobicity while keeping charge constant. In this study, we synthesized a new class of antibacterial oligoTEAs (AOTs) with precise control over backbone hydrophobicity and composition. Our studies suggest that AOTs lyse cells <i>via</i> membrane permeabilization and that hydrophobicity and macromolecular conformation are key properties that regulate AOT activity. Some of our AOTs show highly promising antibacterial activity (MIC ∼ 0.5–5 μM) against clinically relevant pathogens in the presence of serum, with little to no toxicity against RBCs and HEK293 cells. Taken together, our data identify design parameters and criteria that may be useful for assembling the next generation of potent and selective AOTs

Ultrafast Electron Transfer across a Nanocapsular Wall: Coumarins as Donors, Viologen as Acceptor, and Octa Acid Capsule as the Mediator

Results of our study on ultrafast electron transfer (eT) dynamics from coumarins (coumarin-1, coumarin-480, and coumarin-153) incarcerated within octa acid (OA) capsules as electron donors to methyl viologen dissolved in water as acceptor are presented. Upon photoexcitation, coumarin inside the OA capsule transfers an electron to the acceptor electrostatically attached to the capsule leading to a long-lived radical–ion pair separated by the OA capsular wall. This charge-separated state returns to the neutral ground state via back electron transfer on the nanosecond time scale. This system allows for ultrafast electron transfer processes through a molecular wall from the apolar capsular interior to the highly polar (aqueous) environment on the femtosecond time scale. Employing femtosecond transient absorption spectroscopy, distinct rates of both forward (1–25 ps) and backward eT (700–1200 ps) processes were measured. Further understanding of the energetics is provided using Rehm–Weller analysis for the investigated photoinduced eT reactions. The results provide the rates of the eT across a molecular wall, akin to an isotropic solution, depending on the standard free energy of the reaction. The insights from this work could be utilized in the future design of efficient electron transfer processes across interfaces separating apolar and polar environments

Photoinduced Electron Transfer Across a Molecular Wall: Coumarin Dyes as Donors and Methyl viologen and TiO₂ as Acceptors

Coumarins C-153, C-480, and C-1 formed 1:2 (guest:host) complexes with a water-soluble cavitand having eight carboxylic acid groups (OA) in aqueous borate buffer solution. The complexes were photoexcited in the presence of electron acceptors (methyl viologen, MV²⁺, or TiO₂) to probe the possibility of electron transfer between a donor and an acceptor physically separated by a molecular wall. In solution at basic pH, the dication MV²⁺ was associated to the exterior of the complex C-153@OA₂, as suggested by diffusion constants (∼1.2 × 10^–6 cm²/s) determined by DOSY NMR. The fluorescence of C-153@OA₂ was quenched in the presence of increasing amounts of MV²⁺ and Stern–Volmer plots of <i>I</i>_o/<i>I</i> and τ_o/τ vs [MV²⁺] indicated that the quenching was static. As per FT-IR-ATR spectra, the capsule C-153@OA₂ was bound to TiO₂ nanoparticle films. Selective excitation (λ_exc = 420) of the above bound complex resulted in fluorescence quenching. When adsorbed on insulating ZrO₂ nanoparticle films, excitation of the complex resulted in a broad fluorescence spectrum centered at 500 nm and consistent with C-153 being within the lipophilic capsule interior. Consistent with the above results, colloidal TiO₂ quenched the emission while colloidal ZrO₂ did not

Ultrafast Electron Transfer from Upper Excited State of Encapsulated Azulenes to Acceptors across an Organic Molecular Wall

In the context of generating reactive organic radical cations within a confined capsule and exploring photoinduced electron transfer from encapsulated organic molecules to organic and inorganic acceptors through an organic molecular wall, we have investigated electron transfer from the upper excited state (S₂) of azulene (Az) and guaiazulene (GAz) enclosed within an octa acid (OA) capsule to water-soluble 4,4′-dimethyl viologen²⁺ (MV²⁺) and pyridinium⁺ (Py⁺) salts or colloidal TiO₂. S₂ fluorescence of OA encapsulated Az and GAz was quenched by electron acceptors such as MV²⁺ and Py⁺ salts. That electron transfer is responsible for S₂ fluorescence quenching was established by recording the transient absorption spectrum of the MV^●+ in the femtosecond time regime. Femtosecond time-resolved fluorescence experiments suggested that the time constant for the forward and reverse electron transfer from encapsulated Az and GAz to MV²⁺ is 4 and 3.6 ps, and 55.7 and 36.9 ps, respectively. The observed S₂ fluorescence quenching by colloidal TiO₂ in aqueous buffer solution is attributed to electron transfer from encapsulated Az and GAz to TiO₂. Lack of quenching by the wider band gap material ZrO₂ supported the above conclusion. FT-IR-ATR experiments confirmed that OA capsules containing Az and GAz can be adsorbed on TiO₂ films, and excitation of these resulted in S₂ fluorescence quenching. The observations presented here are important in the context of establishing the value of OA type cavitands where charge separation and donor shielding are critical

Synthetic versus Natural Receptors: Supramolecular Control of Chemical Sensing in Fish

The encapsulation of odorants by the synthetic receptor cucurbit[7]­uril (CB[7]) reduces the response of olfactory receptors in Mozambique tilapia (<i>Oreochromis mossambicus</i>) <i>in vivo</i>. For example, the olfactory receptor response to the odorant adamantan-1-amine, as measured by electro-olfactography, was suppressed by 92% in the presence of CB[7]. A reduction in olfactory response of 88% was observed for pentane-1,5-diamine (cadaverine), an odorant associated with carrion avoidance in some fish. The results reveal how the association constants and the concentrations of natural and synthetic receptors play a determinant role and show that synthetic receptors can be used to remove bioactive molecules from fish olfaction

What Is the Optoelectronic Effect of the Capsule on the Guest Molecule in Aqueous Host/Guest Complexes? A Combined Computational and Spectroscopic Perspective

Encapsulation of dye molecules is used as a means to achieve charge separation across different dielectric environments. We analyze the absorption and emission spectra of several coumarin molecules that are encapsulated within an octa-acid dimer forming a molecular capsule. The water-solvated capsule effect on the coumarin’s electronic structure and absorption spectra can be understood as due to an effective dielectric constant where the capsule partially shields electrostatically the dielectric solvent environment. Blue-shifted emission spectra are explained as resulting from a partial intermolecular charge transfer where the capsule is the acceptor, and which reduces the coumarin relaxation in the excited state